Rivastigmine, (S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methyl-phenyl-carbamate is used for treating Alzheimer's disease, and it is useful as an acetylcholinesterase inhibitor in the central nervous system.
Such rivastigmine is commercially available in the form of a patch. GB Patent No. 2,203,040 discloses a transdermal composition in the form of a patch in Example 2, in which the patch is prepared by mixing rivastigmine with two polymers and a plasticizer to obtain a viscous composition, and applying the composition to a foil.
U.S. Pat. No. 6,335,031 discloses a composition for transdermal administration, containing rivastigmine or a salt thereof and an antioxidant as a stabilizer. According to this patent, conventional compositions for transdermal administration which contains rivastigmine are susceptible to degradation even in air-tight packaging due to oxidation by oxygen, making it difficult to secure the storage period required for commercial distribution. Accordingly, in order to solve the above problem, this patent discloses a composition for transdermal administration of rivastigmine, containing an antioxidant such as tocopherol, esters thereof, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole and propyl gallate. Thus, tocopherol has been used as a stabilizer in commercially available products for transdermal administration of rivastigmine.
However, since tocopherol is susceptible to degradation by air or light, it must be kept in cold storage under an inert atmosphere, and since it is present in a liquid form, it is difficult to handle and store during commercial production. In addition, because tocopherol can act as an anticoagulant when administered in vivo, many drug-approved agencies have set a tolerable upper intake level. Therefore, in order to overcome these problems, there is still a need to develop a rivastigmine patch having improved stability.